Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions.

Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.

Cirrhosis in intrahepatic cholangiocarcinoma: prognostic importance and impact on survival.

CONTEXT: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis. OBJECTIVES: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis. METHODS: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis). RESULTS: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival.

Therapeutic Pipeline in Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced stage and disease spectrum including alcoholic hepatitis, a severe manifestation with a high short-term mortality. Corticosteroid, recommended first-line treatment for patients with alcoholic hepatitis, is a very suboptimal treatment. Although the use of early liver transplantation has increased with consistent benefit in select patients with alcoholic hepatitis, its use remains heterogeneous worldwide due to lack of uniform selection criteria. Over the last decade, several therapeutic targets have evolved of promise with ongoing clinical trials in patients with cirrhosis and alcoholic hepatitis. Even with availability of effective medical therapies for alcohol-associated liver disease, long-term outcome depends on abstinence from alcohol use in any spectrum of alcohol-associated liver disease. However, alcohol use disorder treatment remains underutilized due to several barriers even in patients with advanced disease. There is an urgent unmet need to implement and promote integrated multidisciplinary care model with hepatologists and addiction experts to provide comprehensive management for these patients. In this review, we will discuss newer therapies targeting liver disease and therapies targeting alcohol use disorder in patients with alcohol-associated liver disease.

Drug induced autoimmune hepatitis: An unfortunate case of herbal toxicity from Skullcap supplement: A case report.

BACKGROUND: The surge in traditional herbal dietary supplement (HDS) popularity has led to increased drug-induced liver injuries (DILI). Despite lacking evidence of efficacy and being prohibited from making medical claims, their acceptance has risen over sevenfold in the last two decades, with roughly 25% of United States (US) adults using these supplements monthly. An estimated 23000 emergency room visits annually in the US are linked to HDS side effects. NIH-funded research suggests HDS contribute to 7-20% of DILI cases, with similar trends in Europe-Spain reporting 2% and Iceland up to 16%. Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines. Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements, this association appears to be the first documented instance in literature. CASE SUMMARY: A middle-aged Caucasian woman, previously healthy, presented with sudden jaundice. Four months earlier, her liver enzymes were normal. She mentioned recent use of Skullcap mushroom supplements. Tests for chronic liver disease were negative. The first liver biopsy indicated severe resolving drug-induced liver injury. Despite treatment, she was readmitted due to worsening jaundice. Follow-up tests raised concerns about autoimmune hepatitis. A subsequent biopsy confirmed this diagnosis. The patient responded as expected to stopping the medication with improvement in liver enzymes. CONCLUSION: This scenario highlights an uncommon instance of DILI caused by Skullcap supplements. It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. METHODS: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. RESULTS: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1-306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. CONCLUSIONS: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.

Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter.

Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site. Additionally, in contrast to pleural mesothelioma, which has a male predominance (male-female ratio of between four and five to one), women comprise approximately one-half of all cases of malignant peritoneal mesothelioma. A thorough history of occupational/paraoccupational exposure along with histopathology is the key to timely diagnosis and treatment.

Long-Term Outcomes After Transcatheter and Surgical Aortic Valve Replacement in Patients With Cirrhosis: A Guide for the Hepatologist.

BACKGROUND AND AIMS: Hepatologists often determine whether transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is preferred for patients with cirrhosis and severe aortic stenosis. The goal of this cohort study is to compare outcomes following TAVR and SAVR in patients with cirrhosis to inform the preferred intervention. APPROACH AND RESULTS: Prospectively collected data on 105 consecutive patients with cirrhosis and aortic stenosis who underwent TAVR (n = 55) or SAVR (n = 50) between 2008 and 2016 were reviewed retrospectively. Two control groups were included: 2,680 patients without cirrhosis undergoing TAVR and SAVR and 17 patients with cirrhosis who received medical therapy alone. Among the 105 patients with cirrhosis, the median Society of Thoracic Surgeons score was 3.8% (1.5, 6.9), and the median Model for End-Stage Liver Disease (MELD) score was 11.6 (9.4, 14.0). The TAVR group had similar in-hospital (1.8% vs. 2.0%) and 30-day mortality (3.6% vs. 4.2%) as the SAVR group. During the median follow-up of 3.8 years (95% confidence interval, 3.0-6.9), there were 63 (60%) deaths. MELD score (adjusted hazard ratio, 1.13; 95% confidence interval, 1.05-1.21; P = 0.002) was an independent predictor of long-term survival. In the subgroup of patients with MELD score <12, the TAVR group had reduced survival compared with the SAVR group (median survival of 2.8 vs. 4.4 years; P = 0.047). However, in those with MELD score ≥12, survival after TAVR, SAVR, and medical therapy was similar (1.3 vs. 2.1 vs. 1.6 years, respectively; P = 0.53). CONCLUSION: In select patients with cirrhosis, both TAVR and SAVR have acceptable and comparable short-term outcomes. MELD score, but not Society of Thoracic Surgeons score, independently predicts long-term survival after TAVR and SAVR. For patients with MELD score <12, SAVR is a preferred procedure; however, neither procedure appears superior to medical therapy in patients with MELD score ≥12.

Erosive Benign Fibro-osseous Lesion of the External Auditory Canal.

The term fibro-osseous lesion encompasses a spectrum of disorders ranging from inflammatory to neoplastic that microscopically exhibit a connective tissue matrix containing formless trabeculae of compact bone. Characteristically, they are located over healthy bone, from which they are abruptly differentiated. The majority of the lesions arise from the maxillofacial region; the occurrence of a lesion in the external auditory canal (EAC) being extremely rare as is in our case. The lesions present with a range of symptoms ranging from conductive hearing loss, Eustachian tube obstruction to bone erosion that develop due to the mass effect. We report a case of a 35-year-old male patient who presented with insidious onset left aural fullness, decreased hearing followed by intermittent mucopurulent discharge from the ear, who was eventually diagnosed with a benign fibro-osseous lesion of the external auditory canal.

Torsion of an Accessory Hepatic Lobe with Embedded Gallbladder: In an 11-Month-Old Boy.

An accessory lobe of the liver is a rare entity in clinical practice which is diagnosed incidentally. Infrequently, it may present as torsion with a clinical picture of an acute abdomen, a palpable mass, and may be associated with liver function abnormalities. Many of these patients have a history of previous surgery for congenital abdominal wall defects such as omphalocele. We present an extremely rare case of torsion of an accessory hepatic lobe in an 11-month-old male patient who presented in a state of shock. The infant underwent laparotomy and excision of the accessory lobe. Here, we aim to emphasize the importance of prompt management and early resection which is the cornerstone of a favorable outcome.